Understanding process effects on the stability of amorphous form products (recrystallization of amorphous form products)

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Aims:The aim of the project is to understand how various processes influence the stability of drug delivery amorphous form products, in order to limit their recrystallisation. These objectives could roughly be divided into three aspects: Characterisation of model drug delivery systems, prepared via two different routes, and stored in a range of conditionsIdentification of the key molecular factors that affect the stability of the model systems (e.g. designing of experiments)Development of more general predictive models and molecular fingerprints.Methodology:Characterisation of the drug delivery systems is the key aspect of the project. Techniques such as electron microscopy and X-ray diffraction will be used to identify nano-sized crystalline regions within the amorphous state that may initiate re-structuring of the material, and thus lead to product instability. This will allow determination of the size, morphology and structure allowing a tempero-spatial assessment of crystalline areas within the sample. Not only is this process time-dependent but is affected by the type of formulation and processes used to generate the amorphous form. Once reliable methods are developed, a correlation with samples that are developed from different production methods can be developed. The project will also look at simulations and models developed from the characterisation, as they can be utilised to predict formulation properties prior to testing. Predictive models with the established data, would be crucial for predicting the crystallisation of active ingredients and drug delivery systems. Potential Impact: The impact of this project will be in areas where an amorphous product is desired, such as with many drugs within medicine. In this instance, if the products are unstable, and crystallise, this may affect the efficacy. In developing methods to identify, then understand and ultimately predict this crystallisation, we will be able to consider the effects of processing and storage conditions.